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Research Area 1: Regulation of trophoblast homeostasis and differentiation
Trophoblasts are placental-specific epithelial cells meaning they form the outermost layer of the placenta and are fetal cells in direct contact with the maternal environment and cells. We are interested in understanding what the cellular signalling pathways are that control the differentiation of human trophoblasts and their homeostasis. We use a combination of cell models to address our hypotheses including isolated primary human trophoblasts, trophoblast stem cells, organoids, and placental explant models.
Research Area 2: Molecular regulation of trophoblast pyroptosis
We have discovered that the cell that covers the maternal facing surface of the human placenta (the syncytiotrophoblast) undergoes a form of programmed cell death called pyroptosis. The syncytiotrophoblast is a single giant cell that covers the entire maternal-facing placental surface, therefore careful compartmentalization and regulation of pyroptosis is likely necessary to allow for pregnancy progression. We are interested in elucidating the pyroptotic cascade and understanding whether hyper-activation of these pathway contribute to the development of pregnancy complications including preeclampsia and miscarriage. This work is carried out using human trophoblast cell culture models and explants.
Research Area 3: Uterine lining endothelial cell biology
With every reproductive cycle, the uterine vasculature must expand to meet the needs of the newly formed uterine lining and, ultimately, the demands of the fetus and placenta if pregnancy arises. Vascular expansion, or angiogenesis, is governed by the endothelial cells which have tissue specific features and regulation. We are harnessing the power of transcriptomics to identify the tissue specific features of uterine endothelial cells, and the processes that regulate human uterine lining angiogenesis and vascular remodelling. We aim to understand whether insufficient uterine lining angiogenesis plays a causal role in the development of pregnancy complications. This work is carried out using single cell RNA-sequencing, human endothelial cell culture, and animal models.
Research Area 4: Endometrial ageing in advanced age pregnancy
Advanced age pregnancies, or pregnancies in pregnant people >35 years old, represent a growing patient population worldwide. These pregnancies are at a higher risk of pregnancy complications, but it is still unclear why this is the case. It has recently been shown that alterations in the endometrium, or uterine lining, and the poor adaptation of this unique tissue to pregnancy may play an important role in driving increased pregnancy risk in these pregnancies. We aim to understand what differences exist in the cellular composition of the endometrium of advanced age pregnancies compared to young individuals, and to identify therapeutically targetable cellular processes that are altered and may cause poor endometrial adaptation. This work is carried out using single cell RNA-sequencing, spatial biology approaches, and animal models.
We are grateful to the following funding agencies for their support:
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